There is currently a pressing need for innovative ophthalmic dosing systems that compete effectively with ocular dynamic processes. The primary goal for research in this area should be to improve ocular drug penetration through increased bioavailability rather than by the more expedient, but less desirable, approach which is to simply increase total amount of drug instilled. One solution is to design a dosing system that provides prolonged precorneal drug levels. A sustained, low-level drug pool in the preconreal pocket competes more effectively with the lacrimal drainage process than a single pulse dose contining a large amount for drug. Such a prolonged source of drug can be achieved by applying recent successes with covalently binding drugs to a bifunctional polystyrene polymer matrix. The rate of drug release via hydrolytic cleavage can be regulated by controlling the rate of water penetration into the polymer. This is possbile through the choice of appropriate functional groups on the polymer. The drug-polymer matrix will be localized in the precorneal pocket in the form of topically instilled microspheres and drug release and penetration will be quantitated in-vivo using rabbits. Drugs chosen for study are sulfacetamide, fluorometholone and carbenicillin. Research on these structure variations will establish basic guidelines for this system and confirm the versatility and applicability of the proposed dosage form. Preliminary studies in this laboratory have already established the feasibility of placing microspheres into the cul-de-sa. Optimial diameter for retention has been determined to be 9 microns and acute/chronic side effect studies have demonstrated acceptability for the technique. The advantages of a microsphere system vs. a traditional suspension is three-fold: 1) maximal dose retention via singular optimal particle size; 2) release rate is controllable rather than restricted only to drug dissolution rate and 3) particle size is constant so washout of traditional dissovling particles does not occur after dosing. Proposal classification: Recently Trained Investigators; Support of Pilot Studies for Innovative Project.